Cancer-resistant blind mole rat gets genome sequence

The blind mole rat is well adapted to the lack of light and oxygen and other difficulties that arise from its solitary, underground lifestyle

Scientists have sequenced the genome of the blind mole rat, a mammal that digs with its teeth, has skin over its eyes and lives for more than 20 years.

Its underground lifestyle means coping with no light, very little oxygen and an awful lot of dirt.

It is also resistant to cancer, like its distant cousin the naked mole rat.

The new work, published in the journal Nature Communications, will help unpick those secrets and the wider adaptation of animals to difficult environments.

Among the results were what the researchers believe are the genetic signatures of the mole rat's complete loss of vision and its impressive tolerance of low oxygen (or "hypoxia").

They also discovered how its special cancer-fighting mechanism might have evolved.

One of the study's lead authors, Prof Eviatar Nevo from the University of Haifa in Israel, has studied blind mole rats for more than 50 years. In all of that time, a spontaneous tumour has never been discovered.

Even when treated with carcinogenic chemicals, these remarkable rodents were incredibly resistant to cancer.

Evolutionary trade-off

When you have the whole genome, you can more efficiently use the species as a model - for cancer resistance, or adaptation to hypoxia, or other medical challengesDr Denis Larkin, Royal Veterinary College

Most animals rely on cells detecting a cancerous malfunction and shutting themselves down (programmed cell death or "apoptosis"), but the blind mole rat's immune system attacks tumours and causes "necrosis" instead. The new study reports that genes involved in this immune defence have been favoured by evolution, and some have been expanded or duplicated.

All this may have happened because one of the key mediators of the normal cell-shutdown defence, a protein called p53, is mutated in the mole rats as part of their adaptation to low oxygen.

The mole rat spends its entire life under the ground, where oxygen is scarce. In other animals this would send p53 into overdrive.

"When there is low oxygen, in other species, [normal p53] would mean that some cells would die from apoptosis - but not in blind mole rats, because that would be a disaster," said Dr Denis Larkin from the Royal Veterinary College in London, one of the study's authors.

So the mole rats have evolved a unique trade-off, weakening p53 and boosting the immune system's necrotic defence, which "the cancer doesn't know how to deal with," Dr Larkin told BBC News.

The genome study was carried out by a large team of researchers that also spanned China, Israel, the US and Denmark. Dr Larkin was involved in piecing together the evolution of the animal's chromosomes, having done similar work on other genomes ranging from the pig to the yak.

He told the BBC the findings would shift the blind mole rat to "a new level" in the research community. "When you have the whole genome... you can more efficiently use the species as a model - for cancer resistance, or adaptation to hypoxia, or other medical challenges."

The naked mole rat, also studied for its cancer resistance, is a distant relative of the blind mole rat

Dr Philippa Brice, from the genomics think-tank PHG Foundation at the University of Cambridge, told BBC News the mole rats and their "really unusual lifestyle" had already been valuable to scientists studying cancer resistance. She agreed that the genome sequence would mean more rapid progress.

"Now that their complete genome is available, it will make it much easier to probe their unique genetic features, with potential applications for human medical research," Dr Brice said.

The blind mole rat (the newly sequenced species is Spalax galili) is only distantly related to the naked mole rat (Heterocephalus glaber), another unusual, subterranean critter with remarkable cancer resistance.

Their evolutionary histories diverged over 70 million years ago, according to calculations in the new study, and the two mole rats adapted completely separately to life underground.

In fact, the furry-but-blind Spalax is a closer cousin to the common house mouse than to the "sabre-toothed sausage" lookalike Heterocephalus.